Significant efforts have been devoted to the development of nanoparticular delivering systems targeting tumors. However, clinical applications of nanoparticles is hampered by insufficient size homogeneity, difficulties in reproducible synthesis and manufacturing, frequent high uptake in the liver, systemic toxicity of the carriers (particularly for inorganic nanoparticles) and insufficient selectivity for tumor cells. We have recently discovered the ability of properly modified transmembrane peptides to assemble into remarkably uniform spherical nanoparticles with innate biological activity. Self-assembly is driven by a structural transition of the peptide that adopts predominantly a beta-hairpin conformation in aqueous solutions, but folds into an alpha-helix upon spontaneous fusion with cell membrane. Alpha-helical peptide interferes with proper assembly of the target receptor and inhibits its function. The best characterized antagonist inhibits signaling through CXCR4 inhibitor with IC50=100 nM. Addition of polyethylene glycol (PEG) chains of up to 27 monomeric units stabilizes nanoparticles and prevents their superaggregation without interfering with biological activity. Longer PEG chains diminish efficient fusion of nanoparticles with the cell membrane and reduce anti-receptor activity. Nanoparticles efficiently encapsulate poorly soluble hydrophobic drugs, thus providing a unique delivery system with dual anti-tumor activity. Even empty nanoparticles effectively inhibit lung metastasis in a mouse model of human breast tumor, due to their ability to inhibit CXCR4 receptor signaling. We are now in the process of development nanoparticles that fuse with cells in receptor-mediated manner, similar to viruses. Conjugates of self-assebling peptide to ligands of receptors overexpressed on prostate tumors resulted in nanoparticles that fuse more effectively with cells expressing corresponding receptor. Self-assembling virus-like particles with intrinsic biological activity present a new paradigm in anti-cancer drug development.